Cloning and characterization of a high mobility group box 1 (HMGB1) homologue protein from Schistosoma mansoni

Mammalian homologue of high mobility group box chromatin protein (HMGB)1 was identified and cloned from human parasites, Schistosoma mansoni and S. haematobium. Sequence analyses showed that the parasite HMGB1s has 35-40% identity to human and rodent HMGB 1s, and 33% identity to Caenorhabditis elegans HMGB1. Parasite HMGB1s also contains an A box and B box domain similar to mammalian HMGB1, however, it lacks the C-terminal tail that is present in mammalian HMGB1s. Analysis of the expression of HMGB1 in various life cycle stages of S. mansoni reveal S. mansoni HMGB1 (SmHMGB1) as a stage-specific protein, expressed abundantly in egg and adult female stages and at moderate levels in skin-stage schistosomula. Significant levels of SmHMGB1 were also present in excretory secretions of egg stages. Subsequent characterization studies showed that SmHMGB1 is a potent inducer of pro-inflammatory cytokines such as TNF alpha, IL-1R alpha, IL-2R alpha, IL-6, IL-13, IL-13R alpha 1, IL-15 and MIP-1 alpha-from mouse peritoneal macrophages. Pro-inflammatory activity, especially production of TNF alpha-inducing activity, appears to be a function of the B box domain protein. This was confirmed by both real-time reverse transcription PCR and by cytokine ELISA. Thus, results presented in this study suggest that SmHMGB1 may be a key molecule in the development of host inflammatory immune responses associated with schistosomiasis. (c) 2005 Elsevier B.V. All rights reserved.